Communicating with the IBD Patient: How to convey risks and benefits

Transcription

1 Communicating with the IBD Patient: How to convey risks and benefits Corey A. Siegel Assistant Professor of Medicine, Dartmouth Medical School & The Dartmouth Institute for Health Policy and Clinical Practice Director, Dartmouth-Hitchcock IBD Center

2 Risks of IBD Therapy Communicating data with patients Risks of immunomodulators Risks of biologics Are two drugs riskier than one? Risk compared to what?

3 Why are patients so afraid? Unknown Risk Risk Unknown Not Observable New Risk Nuclear accidents Not Dreadful Controllable Equitable Voluntary Aspirin Dreadful Uncontrollable Dread Catastrophic Risk Involuntary Downhill skiing Railroad collisions Slovic P. Perception of Risk. Science Known Risks Observable Old Risk

4 How should we report data to patients? NNT = 7

5 What do you mean by rare and common? Rare 3 per million 20% (median 2%) Common 5% 76% (median 30%) 63% of patients wanted to hear about all lessserious and life-threatening side-effects, even if the chance was less than 1 per 10,000 Siegel CA, et al. Presented at DDW 2011, Chicago, IL.

6 Numbers are hard! Numeracy (quantitative literacy) ½ of patients were unable to convert: 1% to 10 in % of patients were unable to convert: 1 in 1000 to 0.1% Patient have difficulty determining which is the higher risk: 1 in 27 versus 1 in 37 Schwartz LM et al. Ann Intern Med. 1997;127(11): Sheridan SL, Pignone M. Eff Clin Pract. 2002;5:35.

7 Fair and Clear Communication of Risks and Benefits Beware of framing 1,2 Relative risk = 34% reduction in heart attacks Absolute risk = 1.4% reduction in heart attacks 1. Malenka DJ et al. J Gen Intern Med. 1993;8: Hux JE, Naylor CD. Med Decis Making. 1995;5:152-7.

8 Tips for Clear Communication Absolute risks better than relative risk Avoid decimals (0.06%) Keep common denominators (x/10,000) Visual aids help (turn numbers into pictures) Give perspective to other disease & life risks Fagerlin et al. Am J Health Behav Peters et al. Health Affairs 2007.

9 What are the main side-effects of 6MP/Azathioprine? Event Frequency Estimate Stop therapy due to AE 11% Allergic reactions 2% Nausea 2% Hepatitis 2% Pancreatitis 3% Serious infections 5% non-hodgkin s lymphoma 0.04%-0.09% (4-9/10,000) Siegel CA, et al. APT 2005 (weighted average); Siegel CA, et al. CGH 2009; Beaugerie L, et al. Lancet 2009.

10 Solid Tumors and Thiopurines UK study 1994 (Connell, Lancet) 755 azathioprine treated IBD patients No increased risk of solid tumors except slight increase in cervical cancer UK study 2002 (Fraser, APT) Retrospective study including 2204 patients with IBD; 626 exposed to azathioprine 4.5% of patients developed cancer in BOTH groups No increase in colorectal, bronchial or breast CA

11 Risk of Skin Cancer Associated with Thiopurines (CESAME) 19,486 IBD patients 32 cases of skin cancer (20 basal cell, 12 squamous) Look at denominator Wear sunscreen Regular skin checks Fagerlin et al. Am J Health Behav Peters et al. Health Affairs 2007.

12 Adverse Events Associated with anti-tnf Treatment Event Estimated Frequency Stop therapy due to adverse event 10% Infusion or injection site reactions 3%-20% Drug related lupus-like reaction 1% Serious infections 3% Tuberculosis 0.05% (5/10,000) Non-Hodgkin s lymphoma (combo) 0.06% (6/10,000) Multiple sclerosis, heart failure, serious liver injury Case reports only Siegel CA. The risks of biologic therapy for inflammatory bowel disease. In Bernstein, ed. The inflammatory bowel disease yearbook, volume 6. In press; Infliximab package insert; Vermeire Gastro 2003; Cush, Ann Rheum Dis 2005; Lenercept study group, Neurology 1999; ATTACH trial 2003

13 Risk of Dying from Sepsis on Infliximab: Systematic Review Reference Ljung et al. Gut 2004 Study Design Population Based Cohort # Deaths from sepsis thought attributable to infliximab Seiderer et al. Digestion 2004 Single-Center Cohort 0 92 Colombel et al. Gastroenterology 2004 Single-Center Cohort Sands et al. NEJM 2004 Hanauer et al. Lancet 2002 Rutgeerts et al. Gastroenterology 1999 Randomized Controlled Trial Randomized Controlled Trial Randomized Controlled Trial Risk of death from sepsis = 4/1000 pt-yrs # of Patients Siegel et al. Clin Gastroenterol Hepatol. 2006;4:

14 BUT it is a subgroup of patients at this high risk Older Average age = 63 (systematic review); 67 (Mayo) Multiple co-morbidities Concomitant steroids and/or narcotics Long-standing disease Young healthy patients are not in the clear, but probably much less at risk Siegel, CGH 2006; Colombel, Gastro 2004; Lichtenstein CGH 2006; Toruner, Gastro 2008

15 Risk of Other Infections Invasive fungal infections FDA warning 2008 Histoplasmosis, coccidiomycosis, blastomycosis Unrecognized early disease Additional bacterial infections FDA warning 2011 Listeria, Legionella

16 Risk of NH Lymphoma with anti-tnf + IM treatment for Crohn s Disease 8905 patients representing 20,602 pt-years of exposure 13 Non-Hodgkin s lymphomas Mean age 52, 62% male Meta-analysis Results 6.1 per 10,000 pt-years 10/13 exposed to IM* (really a study of combo Rx) NHL rate per 10,000 SIR 95% CI SEER all ages IM alone Anti-TNF + IM vs SEER Anti-TNF+ IM vs IM alone *not reported in 2 Siegel et al, CGH 2009;7:874.

17 Risk of Developing non-hodgkin s Lymphoma Patient receiving Immunomodulator +/- anti-tnf Therapy for 1 year Risk of lymphoma with immune suppression

18 Solid Tumors and anti-tnf Treatment National Data Bank for Rheumatic Diseases ( ) 13,000 patients enrolled, 49% received biologics Type of Cancer Odds Ratio All cancers 1.0 ( ) All solid tumors 1.0 ( ) Colon 0.8 ( ) Lung 1.1 ( ) Breast 0.9 ( ) Pancreas 0.5 ( ) Melanoma 2.3 ( ) Non-melanoma skin 1.5 ( ) Wolfe, Arthritis and Rheumatism 2007;56:2886.

19 Are two drugs riskier than one? Anti-TNF monotherapy versus combination therapy with immunomodulators

20 Are serious infections more common if taking more than 1 medication? TREAT registry Corticosteroids (HR 2.0, 95% CI ) Narcotics (HR 2.7, 95% CI ) Opportunistic infections Prednisone, 6MP/AZA, Infliximab Odds Ratio (95% CI) 1 medication 2.9 ( ) 2 or 3 medications 14.5 (4.9 43) Lichtenstein CGH 2006; Toruner, Gastro 2008

21 Closer look at the Mayo experience with opportunistic infections Number of meds Cases Controls OR (ref) ( ) 2 or (4.9-43) Specific combinations Corticosteroids alone ( ) 6MP/AZA alone ( ) IFX alone ( ) AZA/6MP + steroids (4.5-68) AZA/6MP + IFX (0.1-19) AZA/6MP + IFX + steroids ( ) Toruner et al. Gastro 2008;134:929

22 SONIC Safety Results AZA + placebo (n=161) IFX + placebo (n=163) Risk of infection same with 1 drug or 2 drugs IFX + AZA (n=179) Total (n=503) Pts with > 1 AE, n (%) 138 (85.7%) 139 (85.3%) 156 (87.2%) 433 (86.1%) Pts with > 1 SAE, n (%) 39 (24.2%) 26 (16.0%) 25 (14.0%) 90 (17.9%) Serious infections 8 (5.0%) 4 (2.5%) 6 (3.4%) 18 (3.6%) Sandborn, WJ et al. NEJM 2010.

23 HSTCL It s not how many, it s how often 10 # Cases Anti-TNF + 6MP/AZA 0 Dec 06 Mar 07 Sept 07 April 08 Dec 08 Mar 09 April 10 Feb 11 In ,000 IBD patients treated with infliximab In ,000 IBD patients treated with infliximab Over 400,000 IBD patients treated with infliximab worldwide Centocor, data on file.

24 Natalizumab Smarter use with the JC Virus Antibody Test Anti-JCV Antibody Status Negative Positive (and prior IS use) < 0.11/ years 1.2/ years 8.1/1000 (1 in 125) To ORDER anti-jc Virus antibody test: Quest Labs test # 90257, JC Virus Antibody with Reflex Inhibition Assay About 50% of Crohn s patients will be positive Pepio et al. DDW 2011; Abstract # 1211

25 Compared to what? What puts patients at the most risk treatment or the disease (or life) itself?

26 Don t forget about prednisone Event Any side-effect leading to stopping prednisone Estimated Frequency 55% Ankle swelling 11% Facial swelling 35% Easy bruising 7% Acne 50% Memory problems 7% Psychosis - confusion/agitation 1% Infections 13% Cataracts 9% Increased intraocular pressure 22% High blood pressure 13% Osteoporosis 33% Diabetes Chance increases 10x Present IBD 2001, Rutgeerts APT 2001, Rutgeerts NEJM 1994

27 Risk of Mortality in Crohn s with Severe Disease & Steroids Retrospective cohort from UK (GPRD) 5,539 patients with Crohn s; 41,624 controls Hazard Ratio for the risk of dying Exposure Hazard Ratio 95% CI Crohn s (mild) Crohn s (severe) Current prednisone Current AZA/6MP Lewis et al, AJG 2008;103:1428.

28 Putting Risk in Perspective Over a lifetime, the chance of dying from: Lightning Bicycling accident Drowning Car accident Cancer Heart disease Odds of Dying, National Safety Council. Available at: Accessed July 22, 2006.

29 Maximal Acceptable Risk (Annual %) Most patients are willing to take these risks PML N = 580 Serious infection Lymphoma Moderate to Mild Moderate to Remission Severe to Moderate Severe to Mild Severe to Remission Risk of dying from PML or lymphoma < 1 per 1000 Johnson et al. Gastroenterology 2007.

30 Summary: Risks of IBD Therapy IMs and biologics are associated with real, but small risks of serious adverse events Combination therapy does not appear to increase risk significantly Patients are willing to accept risk, as long as there is substantial benefit Clear communication to patients is critical

31 Life is full of risks, and many are worth taking